PCB 118 induces ultrastructural alterations in the rat liver.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that bioaccumulate in the food chain and thus pose a health risk to humans and other animals. In this study, PCB 118 was added to the diets of Sprague Dawley rats for 13 weeks in concentrations of 2, 20, 200, 2000 p.p.b. to the females and 10, 100, 1000 and 10000 p.p.b. to the males. The chemical was dissolved in corn oil; animals that served as the control received corn oil in the diets devoid of PCB. Use of transmission electron microscopy and stereology revealed significant (P<0.05) elevation in the mean volume fraction of smooth reticulum profiles (20 p.p.b.), peroxisomes (200, 2000 p.p.b.) and lipid droplets (2000 p.p.b.) in the females. Hepatocytes from the males exhibited a significant increase in the mean volume fraction of lipid droplets at 10000 p.p. b. (P<0.05). Interactions between large quantity of estrogen and the PCB probably would account for more profound alterations in the liver of female Sprague-Dawley rats than in the males.

Screening mammography behavior after a false positive mammogram.

This pilot study describes women's interpretations of the experience of a false positive mammogram followed by a negative biopsy and the impact of this experience on subsequent participation in screening mammography. A 25-min, open-ended telephone interview was administered in 1992 to 30 women over age 39 who had negative biopsies in 1987 preceded by abnormal mammograms. Almost twice as many women reported getting regular mammograms after the biopsy (60%) as did before 1987 (33%). Most received their next mammogram after the biopsy within the recommended interval (73%), and those getting regular mammograms prior to the biopsy experience were more likely than those who did not have a prior habit of undergoing mammography to continue to get them afterwards. These preliminary findings suggest that a negative breast biopsy after a positive mammogram does not reduce a patient's likelihood of undergoing screening in the future. In fact, it may serve as an impetus for increased compliance with screening recommendations.

Serial studies of auditory neurotoxicity in patients receiving deferoxamine therapy.

Visual and auditory neurotoxicity was previously documented in 42 of 89 patients with transfusion-dependent anemia who were receiving iron chelation therapy with daily subcutaneous deferoxamine. Twenty-two patients in the affected group had abnormal audiograms with deficits mostly in the high frequency range of 4,000 to 8,000 Hz and in the hearing threshold levels of 30 to 100 decibels. When deferoxamine therapy was discontinued and serial studies were performed, audiograms in seven cases reverted to normal or near normal within two to three weeks, and nine of 13 patients with symptoms became asymptomatic. Audiograms from 15 patients remained abnormal and four patients required hearing aids because of permanent disability. Since 18 of the 22 patients were initially receiving deferoxamine doses in excess of the commonly recommended 50 mg/kg per dose, therapy was restarted with lower doses, usually 50 mg/kg per dose or less depending on the degree of auditory abnormality, and with the exception of two cases no further toxicity was demonstrated. Auditory deterioration and improvement, demonstrated serially in individual patients receiving and not receiving deferoxamine, respectively, provided convincing evidence for a cause-and-effect relation between deferoxamine administration and ototoxicity. Based on these data, a plan of management was developed that allows effective yet safe administration of deferoxamine. A dose of 50 mg/kg is recommended in those without audiogram abnormalities. With mild toxicity, a reduction to 30 or 40 mg/kg per dose should result in a reversal of the abnormal results to normal within four weeks. Moderate abnormalities require a reduction of deferoxamine to 25 mg/kg per dose with careful monitoring. In those with symptoms of hearing loss, the drug should be stopped for four weeks, and when the audiogram is stable or improved, therapy should be restarted at 10 to 25 mg/kg per dose. Serial audiograms should be performed every six months in those without problems and more frequently in young patients with normal serum ferritin values and in those with auditory dysfunction.

Percutaneous balloon aortic valvuloplasty for aortic stenosis in elderly patients at high risk for surgery.

Six elderly patients had percutaneous balloon aortic valvuloplasty for severe, symptomatic calcific aortic stenosis because valve replacement surgery was considered too risky in five patients with severe coexisting cardiac or other medical problems and because one patient refused to have surgery. The procedure resulted in a significant reduction in the mean (+/-SD) aortic valve gradient, from 47 +/- 13 to 32 +/- 12 mm Hg (change, -32%, p less than 0.01), and a significant increase in the mean area of the aortic valve, from 0.64 +/- 0.12 to 0.90 +/- 0.17 cm2 (change, +40%, p less than 0.001). Blood loss from the femoral puncture site was the only major procedural complication. At a mean follow-up of 2 months after the procedure, all patients were alive and dyspnea had improved by two New York Heart Association functional classes in four patients and by one functional class in two patients. A significant short-term increase in aortic valve area and alleviation in symptoms can be achieved safely by percutaneous balloon aortic valvuloplasty in elderly patients with severe calcific aortic stenosis who are at high risk for surgical complications.

Subclinical VEP abnormalities in patients on chronic deferoxamine therapy: longitudinal studies.

As deferoxamine (DFO) appeared to have certain toxic effects on the sensory pathways in some of our patients on nightly subcutaneous deferoxamine (DFO) for transfusion-dependent anemia, treatment was stopped in all of these patients to obtain a comprehensive baseline assessment of sensory function. Visual evoked potentials (VEPs) were studied in all patients; the 77 described in this report all had normal ophthalmological examinations. Abnormally prolonged VEP latencies were found in 21%. The patients remained off DFO for 2-6 months, and most of those with abnormal VEPs who were retested showed improvement in their VEPs over this period with the VEPs returning to within normal range in half the cases; two showed no change. Since restarting DFO, VEP latencies in 10 of these patients have increased again beyond normal limits, as have the VEPs in 7 who had previously normal VEPs. Although most of the 77 patients have VEPs that are currently normal and stable while on DFO, a significant sub-group have abnormal VEPs that appear sensitive to the administration of DFO and may reflect a vulnerability to DFO neurotoxicity. These data suggest that the VEPs can detect subclinical toxic effects of DFO on the visual system and should be considered as a monitor for patients receiving chronic DFO therapy.

Bile duct strictures associated with hepatic arterial infusion chemotherapy.

We report 6 cases of bile duct strictures in patients receiving intraarterial floxuridine chemotherapy for metastatic colon carcinoma. The computed tomographic and cholangiographic features of these cases mimic those seen with primary sclerosing cholangitis. The postulated mechanism for development of biliary strictures is direct toxicity and/or occlusion of the peribiliary vascular plexus with resultant biliary fibrosis.

Sequelae of injury to the heart caused by multiple needles.

A case is reported in which multiple needles were inserted into the heart by a patient, resulting in the unusual combination of a coronary artery-cameral fistula to the left ventricle, an intramural defect of the left ventricular free wall and a ventricular septal defect. This unique lesion was suspected on the basis of two-dimensional and Doppler echocardiography and contrast computed tomographic imaging. Its presence was confirmed during cardiac catheterization and cineangiography.

Visual and auditory neurotoxicity in patients receiving subcutaneous deferoxamine infusions.

Of 89 patients receiving nightly subcutaneous deferoxamine for transfusion-dependent thalassemia major or Diamond-Blackfan anemia, 13 presented with visual loss or deafness of acute onset or both. Detailed ophthalmologic, audiologic, and evoked-potential studies uncovered abnormalities caused by neurotoxicity in 27 more. Four patients with visual loss had optic neuropathy, with a marked decrease in acuity, loss of color vision, and delayed visual evoked potentials. Five asymptomatic patients had changes in the pigment of the retinal epithelium. The hearing loss was characterized by a high-frequency sensorineural deficit, which necessitated hearing aids in six patients. When deferoxamine was stopped, recovery of vision was complete in 2 patients and partial in 2, and in 22 patients with abnormal audiograms, reversal of the hearing deficit was complete in 4 and partial in 1. An analysis of the clinical data showed that members of the affected group were younger, had lower serum ferritin values, and were self-administering higher doses of deferoxamine per kilogram of body weight. Significantly lower doses of deferoxamine were being taken by patients without abnormalities than by those with visual symptoms, abnormal audiograms, or prolonged evoked potentials (P less than 0.001, less than 0.006, and less than 0.04, respectively). The data implicate high-dose deferoxamine as a central factor in the pathogenesis of the neurotoxicity. We strongly recommend careful regulation of the deferoxamine dosage and serial audiovisual monitoring in all patients receiving the drug.

Acute mesenteric ischemia: angiographic spectrum.

Fifty-six patients, selected by clinical criteria, underwent angiography for suspected acute mesenteric ischemia. Twenty-nine patients subsequently did not have mesenteric ischemia and had negative arteriograms. Twenty-seven patients had mesenteric ischemia: arterial thrombosis (three), arterial embolus (seven), venous thrombosis (five), vasculitis with thrombosis (one), and nonocclusive ischemia (11). Of these 27 patients, 12 (44%) received intraarterial vasodilator infusions. Overall, 13 (48%) of the 27 patients survived their hospitalization, including five (45%) of 11 with nonocclusive ischemia. This experience confirms that nonocclusive ischemia is the most common form of the disorder diagnosed by angiography. Most patients with mesenteric ischemia are candidates for intraarterial vasodilator therapy. Early angiography in patients with suspected acute mesenteric ischemia permits early diagnosis and differentiation between occlusive and nonocclusive types. Interventional infusion therapy may improve survival.

Primary chylopericardium: the role of lymphangiography.

Primary chylopericardium is often a benign asymoptomatic disease, but patients with associated mediastinal lymphatic tumors may develop cardiac tamponade. Lymphangiography demonstrates mediastinal lymphatic abnormalities in these high risk patients on whom subtotal pericardiectomy and thoracic duct ligation should be performed. Since such tumors have been found in half of reported cases and because extrathoracic lymphangiomas may coexist, lymphangiography with skeletal survey is recommended in all cases. These conclusions are based on a review of 31 published cases and an additional case of our own. Lymphangiographic findings were available in 17 of these patients.